Cocaine has been an abused drug for centuries. The ability to measure cocaine and cocaine metabolites, therefore, is vital to many medical and clinical ends, including the treatment of cocaine addiction.
Cocaine is rapidly metabolized in the body to primarily benzoylecgonine and ecgonine. In cases where alcohol (ethanol) consumption is also associated with cocaine use, the cocaine is also metabolized to benzoylecgonine ethyl ester and related aryl hydroxy metabolites (see, e.g., J. Anal. Toxicol. 8:38-42 (1984) and J. Anal. Toxicol. 3:59-63 (1979)). The benzoylecgonine ethyl ester and related metabolites have been identified to be more potent than cocaine and related metabolites and are believed to be responsible for deaths associated with simultaneous alcohol and cocaine use. Accordingly, there is a medical need for antibodies and diagnostics to rapidly detect benzoylecgonine ethyl ester and related metabolites.
The preparation of antibodies to cocaine and cocaine metabolites requires that a cocaine derivative be synthesized so that attachment to an antigenic polypeptide or protein is possible. In addition, the cocaine derivative is attached to various polypeptides, proteins or labels for use in screening antibodies and in the immunoassay process. The cocaine derivative should mimic the structure of the cocaine metabolite sought to be measured. Therefore, the selection and synthesis of the types of cocaine derivatives for attachment to proteins, polypeptides or labels is critical. In addition, the cocaine derivatives need to be stable to hydrolysis which might occur in an aqueous solution.